In recent years, whole-body circulation has come to be assisted through the use of an artificial heart or the like if cardiac function is compromised owing to conditions such as heart failure or the like. Ventricular assist devices can temporarily replace the cardiac function, lost on account of, for instance, heart disease, external injury, or heart attack, until recovery of the cardiac function or while waiting for a heart transplant, or can replace cardiac function permanently, thereby keeping the patient alive, all of which underscore the importance of such devices.
In particular, it is well known that left ventricular assist devices are extremely effective for ameliorating symptoms in patients of congestive heart failure. Left ventricular assist devices have been developed as a last-resort therapy for patients of severe congestive heart failure, for instance, patients who cannot undergo a heart transplant either temporarily or permanently, and who require long-term circulatory support. Left ventricular assist devices can assume the function of the left ventricle, namely, pumping into the whole body the blood that has taken up oxygen in the lungs. A left ventricular assist device is attached to the heart and blood vessels of the patient, and can be removed once the natural heart has recovered.
Ordinary ventricular assist devices comprise mainly, for instance, devices or instruments such as a blood pump, a controller, a battery, a cannula, an outflow graft and the like. The foregoing are surgically implanted in the thoracic cavity of the patient. To do so, a cannula is inserted into a ventricle (left or right ventricle) or an atrium (left or right atrium), blood is drained, blood flow is started by a blood pump, and blood is returned to the aorta via an outflow graft. The above procedure allows securing blood circulation in a patient with impaired cardiac function.
Artificial hearts and ventricular assist devices dwell in the body for long periods of time, and hence the devices or instruments that make up the foregoing must possess such mechanical strength as allows them to retain a stable structure when implanted in vivo for long periods of time. Should part of such device or instrument be damaged and release, as a result, fragments or the like into the bloodstream, an embolism may occur. Therefore, mechanical strength must be rigorously guaranteed.
In addition to the above-described mechanical strength issue, long-term use of an artificial heart or a ventricular assist device is complicated by the serious problem of circulatory deficit caused by thrombi. For instance, a thrombus forming and growing in the blood pump may occlude blood flow passages or cause the pump to stop. Even if the thrombus is very small, detachment thereof might occlude a peripheral blood vessel, thereby posing significant danger to life. For the purpose of avoiding such problem, the devices, instruments and so forth comprised in artificial hearts and ventricular assist devices have used conventionally antithrombogenic materials, or materials the surface of which is provided with some antithrombogenic means.
However, even if such materials are used in the devices or instruments that make up an artificial heart or a ventricular assist device, thrombi tend to form readily, for example, on the outer peripheral face of a cannula which is inserted into the heart, i.e., on the outer peripheral face of an inflow cannula. This thrombus formation tendency on the outer peripheral face of an inflow cannula arises from the blood pooling in the gap which forms between the outer peripheral face of the inflow cannula and the inner wall of the own heart since the inflow cannula is disposed so as to protrude into a ventricle (left or right ventricle) or an atrium (left or right atrium), and from the blood's property of being prone to coagulate at slow flow sites. In actuality, it has been found that insertion into the heart of a conventionally used inflow cannula made of titanium and having a smooth surface, i.e., having the surface smoothed by polishing or the like, may result in formation of thrombi on the surface of the cannula within a short period of time. If a thrombus detaches in the left ventricle or the like, it enters the bloodstream at once and is carried into the body, where it may cause an infarction in a thin blood vessel. This may give rise to conditions, such as cerebral infarction or renal infarction, that have a devastating impact on the patient. The same problem besets devices or instruments other than the inflow cannula, such as blood pumps (in particular, the pump inner surface that is in contact with the blood), connectors or the like that make up as well an artificial heart or a ventricular assist device, and which are indwelling at sites where blood pools easily.
To deal with the above problem, the blood-contacting surface of devices or instruments that make up a ventricular assist device is provided with a textured surface, i.e., a surface formed with irregularities or pores, or alternatively, a structure having a textured surface is separately arranged and fixed onto the blood-contacting surface of the above devices or instruments, as an attempt at anchoring thrombi stably by way of the irregularities and/or pores of the textured surface, in particular, by way of the voids formed in the pores. Such thrombus anchoring should allow preventing thrombi from getting into the blood, while allowing endothelial cells to be adhered onto the anchored thrombi, depending on the sites at which the above textured surface is provided. As is known, endothelial cells exhibit very high antithrombogenicity. Ultimately, covering with endothelial cells the entire blood-contacting surface in the ventricular assist device would therefore be ideal in terms of preventing thrombus formation.
As an example of a ventricular assist device using such a textured surface, H. Harasaki et al. (H. Harasaki et al. Powdered Metal Surface for Blood pump. Trans Am Soc Artif Intern Organs, 1979; 25; 225-230) discloses a pulsatile blood pump, the surface of which is coated with sintered titanium alloy spheres. In the blood pump by Harasaki et al., multiple titanium alloy spheres are sintered onto the surface of the blood pump, to form thereby, on the blood pump, a textured surface comprising the sintered titanium alloy spheres. It is observed therein that the best anchoring effect is achieved when using titanium alloy spheres having a particle size distribution lying within 75 to 150 micrometer. In this regard, it has been found that the pores, which are formed between the spheres when using multiple spheres having such a particle size range, have an opening surface area of about not less than 0.22×10−3 mm2 (if converted to equivalent circular diameter, this opening surface area yields a diameter of about 17 micrometer), when performing calculations under the assumption that all the spheres are arranged regularly, and the pores formed between spheres are smallest when spheres having the smallest particle size (75 micrometer) are arrayed in a dense packing.
U.S. Pat. No. 6,050,975 discloses a blood pump using a textured surface in some components. Here also, as is the case in H. Harasaki et al., the textured surface used is a sintered titanium sphere layer formed by sintering titanium spheres onto the surface of the component.
US2007/0299297 A1 discloses an axial flow pump of a type in which the blood pump is inserted directly into the left ventricle, such that a structure having a sintered titanium microsphere layer is arranged on the outer peripheral face of the blood pump that comes into contact with blood. In this case as well, the sintered titanium microsphere layer plays the role of a textured surface. In the blood pump disclosed in US2007/0299297 A1, however, the titanium microspheres are sintered onto a member called a “wall shell”, independently from the blood pump, after which the wall shell having the sintered titanium microsphere layer is fitted onto the outer peripheral face of the blood pump.
As described above, covering the entire blood-contacting surface of a ventricular assist device with endothelial cells, by way of a textured surface, would be ideal in terms of antithrombogenicity. However, the number of cell divisions that endothelial cells can undergo is limited in practice, and hence endothelial cells do not reach up to sites that are removed at a distance from living tissue. Therefore, covering the entire blood-contacting surface in the ventricular assist device with endothelial cells is next to impossible. Thus, even if part of the blood-contacting surface were covered with endothelial cells when using a textured surface over the entire blood-contacting surface, there would still remain other sites uncovered with the endothelial cells. Should germs get mixed with the blood, the textured surface sites not covered with endothelial cells will become breeding grounds for germs within the textured surface. Once germs have become established there, the affected sites are very unlikely to be reverted to a normal state. Removing the germs with antibiotics or the like is difficult, and sepsis may set in over time.
In practical terms, therefore, it is fair to say that the best ventricular assist device design at present involves using a textured surface only at required sites within the blood-contacting surface of the ventricular assist device, with thrombus anchoring being carried out only at these sites, and/or with endothelial cells covering only these sites, while other sites have a minor-surface finish and/or are coated with an antithrombogenic coating. In light of the above, there is no doubt that, as well as being capable of manufacturing a ventricular assist device by appropriately selecting a smooth surface or a textures surface for each device, instrument, or component that makes up the ventricular assist device, it is also necessary to make it possible to manufacture a device, instrument, or component that comprises mixed textured surface portions and smooth surface portions.